from Part III - Growth hormone replacement therapy in adults with growth hormone deficiency
Published online by Cambridge University Press: 08 January 2010
Introduction
Until a few years ago, growth hormone (GH) and its principal mediator, insulinlike growth factor-I (IGF-I), were considered essential only to the control of linear growth, glucose homeostasis and for the maintenance of skeletal muscle mass (De Boer, Blok & Van der Veen, 1995). In the past decade, a series of animal and human studies have unequivocally proven that the heart is a target organ for the GH/IGF-I axis, which modulates cardiac structure and function (Timsit et al., 1990; Castagnino et al., 1992; Jin et al., 1995; Duerr et al., 1996; Fazio et al., 1996b, c; Anker et al., 1997a, b; Cittadini et al., 1997b; Volterrani et al., 1997).
In this chapter, we will: (a) provide molecular evidence for the interaction between GH and the heart; (b) describe cardiac morphology and function in conditions of GH excess and deficiency; (c) discuss GH regulation of cardiac function; and finally (d) give an overview of the therapeutic potential of GH in cardiovascular medicine.
Molecular basis of GH interaction with the heart
The possibility that GH and IGF-I interact with a target organ requires the presence of specific receptors. Indeed, the heart possesses the main prerequisites for an endocrine as well as a autocrine/paracrine action of GH and IGF-I: (a) GH receptors are expressed in the heart (Mathews, Enberg & Norstedt, 1989), to a greater extent than in other tissues; (b) IGF-I receptors are present in both neonatal and adult cardiomyocytes (Guler et al., 1988; Engelmann et al., 1989); and (c) local production of IGF-I has been documented at both gene and protein level (D'Ercole, Stiles & Underwood, 1984).
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